LP-168 / Lupeng Pharma - LARVOL DELTA

An open label, single arm, multicenter phase II study of the efficacy and safety of LP-168 monotherapy for relapsed or refractory mantle cell lymphoma. (ASCO 2024) - P2 | "Clinical Trial Registration Number: NCT05716087"

Clinical • Monotherapy • P2 data • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology

LP-168-CN301: Phase Ib Study of Rocbrutinib in Combination With R-CHOP in Patients With Newly Diagnosed B-cell Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=112 | Recruiting | Sponsor: Guangzhou Lupeng Pharmaceutical Company LTD. | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

The Mass Balance Study of LP-168 in Healthy Subjects (clinicaltrials.gov) - P1 | N=6 | Completed | Sponsor: Guangzhou Lupeng Pharmaceutical Company LTD. | Active, not recruiting ➔ Completed

Trial completion

The Mass Balance Study of LP-168 in Healthy Subjects (clinicaltrials.gov) - P1 | N=6 | Active, not recruiting | Sponsor: Guangzhou Lupeng Pharmaceutical Company LTD. | Recruiting ➔ Active, not recruiting

Enrollment closed

Phase Ib Study of Rocbrutinib in Combination With R-CHOP in Patients With Newly Diagnosed B-cell Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=112 | Not yet recruiting | Sponsor: Guangzhou Lupeng Pharmaceutical Company LTD.

New P1 trial • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Pre-Clinical Evaluation of a New-Generation Orally Bioavailable Dual Bcl-2/Bcl-Xl Inhibitor LP-118 in Mantle Cell Lymphoma (ASH 2023) - "For in vivo experiments, Granta519 and REC-1-derived xenograft models were established and treated with different regimens: for Granta519 model, mice were treated with vehicle, BR (bendamustine, 25mg/kg, iv, day 1 and rituximab, 10mg/kg, iv, day 1), LP-118 (75mg/kg, po, qd, 28 days) in combination with BR...In the matrix combination studies with REC-1 cells, combinations of LP-118 with SOC agents showed synergistic anticancer effects with all the tested drugs, including vincristine, bendamustine, cytarabine, docetaxel, doxorubicin, cisplatin, and bortezomib...Similarly, the combination of LP-118 with LP-168 (BTKi) also resulted in complete tumor regression in REC-1 xenograft models at day 40, while the combination of ABT-199 plus ibrutinib showed no significant tumor growth inhibition, suggesting that combination of LP-118 and LP-168, a new generation BTKi currently also in clinical trial, might be more effective against MCL than the combination of ABT-199 plus ibrutinib..."

IO biomarker • Preclinical • Hematological Disorders • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • Solid Tumor • BCL2 • BCL2L1

The Mass Balance Study of LP-168 in Healthy Subjects (clinicaltrials.gov) - P1 | N=8 | Recruiting | Sponsor: Guangzhou Lupeng Pharmaceutical Company LTD. | Not yet recruiting ➔ Recruiting

Enrollment open

Safety and Efficacy Results from the Phase I Study of a Novel Dual Covalent and Non-Covalent Next Generation Inhibitor of Bruton's Tyrosine Kinase LP-168 in Patients with Relapsed/Refractory Mantle Cell Lymphoma (ASH 2023) - P1, P2 | "All patients have received rituximab or a rituximab-containing regimen. In this Phase 1 trial, the novel BTK inhibitor LP-168 demonstrated a high CR rate and durable response in heavily pre-treated R/R MCL including blastoid/pleomorphic variant with favorable safety. Moreover, LP-168 could effectively overcome the acquired resistance to prior cBTKi. Based on the safety, PK and preliminary efficacy data from the Phase 1 study so far, we have determined the recommended phase 2 dose (RP2D) for MCL as 150 mg QD."

Clinical • P1 data • Anemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • Respiratory Diseases

Initial Results of a Phase 1 Dose Escalation Study of LP-168, a Novel Covalent and Non-Covalent Next-Generation Inhibitor of Bruton's Tyrosine Kinase (ASH 2023) - P1 | "Covalent BTKi (cBTKi) including ibrutinib, acalabrutinib, and zanubrutinib, share a common resistance mechanism, acquisition of a C481 mutation in BTK. LP-168 has been well tolerated in this study, with no DLTs identified at doses up to 300 mg daily. Preliminary efficacy was observed in high risk CLL pts, including those treated with one or more BTKi. Considering safety, efficacy, and PK/PD, dose expansion will occur at 200 mg and 300 mg daily following the FDA Project Optimus guidelines to determine the recommended phase 2 dose."

P1 data • Atrial Fibrillation • Cardiovascular • Cerebral Hemorrhage • Chronic Lymphocytic Leukemia • CNS Disorders • Constipation • Cough • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Hypertension • Leukemia • Lymphoma • Mantle Cell Lymphoma • Musculoskeletal Pain • Oncology • Pain • Respiratory Diseases • PLCG2 • TP53

Targeting Covalent and Non-Covalent Btki-Resistant CLL Using the Dual Irreversible/Reversible 4th Generation BTK Inhibitor LP-168 (ASH 2023) - P1 | "Pirtobrutinib and nemtabrutinib are non-covalent BTK inhibitors (ncBTKi) developed to target and inhibit C481S mutant BTK...We treated mice daily via oral gavage and found that 50 mg/kg of LP-168 significantly improved survival in the Eµ-TCL1 model when compared to vehicle (median 51 vs 44 days; p=0.0018) or ibrutinib at 50 mg/kg (median 51 vs 45 days; p=0.0098) and the Eµ-MTCP1 model when compared with vehicle (median 122 vs 62 days; p<0.0001) or ibrutinib at 50 mg/kg (median 122 vs 96 days; p=0.0162) (Figure 1B). Collectively, our data demonstrate that LP-168 is a potent and selective inhibitor of BTK with activity against CLL, even in the presence of mutations that mediate resistance to cBTKi and ncBTKi. These data support the continued preclinical and clinical investigation of LP-168, which is currently being studied in the phase 1 setting of CLL (NCT04775745) and NHL (NCT04993690)."

Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • ANXA5 • CCL3 • CXCL12 • CXCL13 • CXCL14 • PLCG2

A Novel Dual Covalent and Non-Covalent Next Generation Inhibitor of Bruton's Tyrosine Kinase LP-168 in Patients with Relapsed/Refractory B Cell Non-Hodgkin Lymphoma: Safety and Efficacy Results from a Phase 1 Study (ASH 2023) - P1 | "The current results of the Phase 1 study showed that LP-168 was well tolerated at 100-200 mg QD with favorable PK profile and has demonstrated encouraging efficacy in multiple B-cell malignancies, including those who had progressed on prior cBTKi."

Clinical • P1 data • Anemia • Atrial Fibrillation • Cardiovascular • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Hypertension • Infectious Disease • Leukemia • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pancreatitis • Respiratory Diseases • Small Lymphocytic Lymphoma

Study of Oral Administration of LP-168 in Patients With Relapsed or Refractory B-cell Malignancies. (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: Newave Pharmaceutical Inc | Trial completion date: Jul 2023 ➔ Dec 2025 | Trial primary completion date: Jul 2023 ➔ Jul 2025

Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hairy Cell Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia

The Mass Balance Study of LP-168 in Healthy Subjects (clinicaltrials.gov) - P1 | N=8 | Not yet recruiting | Sponsor: Guangzhou Lupeng Pharmaceutical Company LTD.

New P1 trial

A Study of LP-168 in Participants With Relapse or Refractory B-Cell Lymphoma (clinicaltrials.gov) - P1 | N=156 | Recruiting | Sponsor: Guangzhou Lupeng Pharmaceutical Company LTD. | Trial completion date: Dec 2023 ➔ Jun 2024 | Trial primary completion date: Jul 2023 ➔ Dec 2023

Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Food Effect Study of LP-168 Tablets in Healthy Subjects (clinicaltrials.gov) - P1 | N=22 | Completed | Sponsor: Guangzhou Lupeng Pharmaceutical Company LTD. | Recruiting ➔ Completed

Trial completion • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology

A Study of LP-168 in Participants With Relapse or Refractory Mantle Cell Lymphoma (clinicaltrials.gov) - P2 | N=62 | Recruiting | Sponsor: Guangzhou Lupeng Pharmaceutical Company LTD. | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology

A Food Effect Study of LP-168 Tablets in Healthy Subjects (clinicaltrials.gov) - P1 | N=22 | Recruiting | Sponsor: Guangzhou Lupeng Pharmaceutical Company LTD. | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology

A Food Effect Study of LP-168 Tablets in Healthy Subjects (clinicaltrials.gov) - P1 | N=22 | Not yet recruiting | Sponsor: Guangzhou Lupeng Pharmaceutical Company LTD.

New P1 trial • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology

A Study of LP-168 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=70 | Completed | Sponsor: Guangzhou Lupeng Pharmaceutical Company LTD. | Recruiting ➔ Completed

Trial completion • CNS Disorders • Multiple Sclerosis • Neuromyelitis Optica Spectrum Disorder

A Study of LP-168 in Participants With Relapse or Refractory Mantle Cell Lymphoma (clinicaltrials.gov) - P2 | N=62 | Not yet recruiting | Sponsor: Guangzhou Lupeng Pharmaceutical Company LTD.

Monotherapy • New P2 trial • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology

A Study of LP-168 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=70 | Recruiting | Sponsor: Guangzhou Lupeng Pharmaceutical Company LTD.

New P1 trial • CNS Disorders • Multiple Sclerosis • Neuromyelitis Optica Spectrum Disorder

A Study of LP-168 in Participants With Relapse or Refractory B-Cell Lymphoma (clinicaltrials.gov) - P1; N=156; Recruiting; Sponsor: Guangzhou Lupeng Pharmaceutical Company LTD.

New P1 trial • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Study of Oral Administration of LP-168 in Patients With Relapsed or Refractory B-cell Malignancies. (clinicaltrials.gov) - P1; N=60; Recruiting; Sponsor: Newave Pharmaceutical Inc; Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hairy Cell Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia

Study of Oral Administration of LP-168 in Patients With Relapsed or Refractory B-cell Malignancies. (clinicaltrials.gov) - P1; N=60; Not yet recruiting; Sponsor: Newave Pharmaceutical Inc

Clinical • New P1 trial • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hairy Cell Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia